Analysis of CTCL cell lines reveals important differences between mycosis fungoides/Sézary syndrome vs. HTLV-1+ leukemic cell lines

Elena Netchiporouk; Jennifer Gantchev; Matthew Tsang; Philippe Thibault; Andrew K. Watters; John Douglas Matthew Hughes; Feras M. Ghazawi; Anders Woetmann; Niels Ødum; Denis Sasseville; Ivan V. Litvinov

doi:10.18632/oncotarget.21619

Analysis of CTCL cell lines reveals important differences between mycosis fungoides/Sézary syndrome vs. HTLV-1⁺ leukemic cell lines

Elena Netchiporouk, Jennifer Gantchev, Matthew Tsang, Philippe Thibault, Andrew K. Watters, John Douglas Matthew Hughes, Feras M. Ghazawi, Anders Woetmann, Niels Ødum, Denis Sasseville, Ivan V. Litvinov^*

^*Corresponding author for this work

22 Citations (Scopus)

174 Downloads (Pure)

Abstract

HTLV-1 is estimated to affect ~20 million people worldwide and in ~5% of carriers it produces Adult T-Cell Leukemia/Lymphoma (ATLL), which can often masquerade and present with classic erythematous pruritic patches and plaques that are typically seen in Mycosis Fungoides (MF) and Sézary Syndrome (SS), the most recognized variants of Cutaneous T-Cell Lymphomas (CTCL). For many years the role of HTLV- 1 in the pathogenesis of MF/SS has been hotly debated. In this study we analyzed CTCL vs. HTLV-1⁺ leukemic cells. We performed G-banding/spectral karyotyping, extensive gene expression analysis, TP53 sequencing in the 11 patient-derived HTLV- 1⁺ (MJ and Hut102) vs. HTLV-1- (Myla, Mac2a, PB2B, HH, H9, Hut78, SZ4, Sez4 and SeAx) CTCL cell lines. We further tested drug sensitivities to commonly used CTCL therapies and studied the ability of these cells to produce subcutaneous xenograft tumors in NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ mice. Our work demonstrates that unlike classic advanced MF/SS cells that acquire many ongoing balanced and unbalanced chromosomal translocations, HTLV-1⁺ CTCL leukemia cells are diploid and exhibit only a minimal number of non-specific chromosomal alterations. Our results indicate that HTLV-1 virus is likely not involved in the pathogenesis of classic MF/SS since it drives a very different pathway of lymphomagenesis based on our findings in these cells. This study also provides for the first time a comprehensive characterization of the CTCL cells with respect to gene expression profiling, TP53 mutation status, ability to produce tumors in mice and response to commonly used therapies.

Original language	English
Journal	OncoTarget
Volume	8
Issue number	56
Pages (from-to)	95981-95998
Number of pages	18
ISSN	1949-2553
DOIs	https://doi.org/10.18632/oncotarget.21619
Publication status	Published - 2017

Keywords

Cutaneous T-cell lymphomas
Gene expression analysis
Human T-cell lymphotropic virus type 1
Spectral karyotyping
Xenograft tumors

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10.18632/oncotarget.21619Licence: CC BY

Analysis of CTCL cell lines reveals important differences between mycosis fungoides/Sézary syndrome vs. HTLV-1+ leukemic cell linesFinal published version, 5.14 MBLicence: CC BY

Cite this

Netchiporouk, E., Gantchev, J., Tsang, M., Thibault, P., Watters, A. K., Hughes, J. D. M., Ghazawi, F. M., Woetmann, A., Ødum, N., Sasseville, D., & Litvinov, I. V. (2017). Analysis of CTCL cell lines reveals important differences between mycosis fungoides/Sézary syndrome vs. HTLV-1⁺ leukemic cell lines. OncoTarget, 8(56), 95981-95998. https://doi.org/10.18632/oncotarget.21619

Netchiporouk, E, Gantchev, J, Tsang, M, Thibault, P, Watters, AK, Hughes, JDM, Ghazawi, FM, Woetmann, A , Ødum, N, Sasseville, D & Litvinov, IV 2017, 'Analysis of CTCL cell lines reveals important differences between mycosis fungoides/Sézary syndrome vs. HTLV-1⁺ leukemic cell lines', OncoTarget, vol. 8, no. 56, pp. 95981-95998. https://doi.org/10.18632/oncotarget.21619

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title = "Analysis of CTCL cell lines reveals important differences between mycosis fungoides/S{\'e}zary syndrome vs. HTLV-1+ leukemic cell lines",

abstract = "HTLV-1 is estimated to affect ~20 million people worldwide and in ~5% of carriers it produces Adult T-Cell Leukemia/Lymphoma (ATLL), which can often masquerade and present with classic erythematous pruritic patches and plaques that are typically seen in Mycosis Fungoides (MF) and S{\'e}zary Syndrome (SS), the most recognized variants of Cutaneous T-Cell Lymphomas (CTCL). For many years the role of HTLV- 1 in the pathogenesis of MF/SS has been hotly debated. In this study we analyzed CTCL vs. HTLV-1+ leukemic cells. We performed G-banding/spectral karyotyping, extensive gene expression analysis, TP53 sequencing in the 11 patient-derived HTLV- 1+ (MJ and Hut102) vs. HTLV-1- (Myla, Mac2a, PB2B, HH, H9, Hut78, SZ4, Sez4 and SeAx) CTCL cell lines. We further tested drug sensitivities to commonly used CTCL therapies and studied the ability of these cells to produce subcutaneous xenograft tumors in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice. Our work demonstrates that unlike classic advanced MF/SS cells that acquire many ongoing balanced and unbalanced chromosomal translocations, HTLV-1+ CTCL leukemia cells are diploid and exhibit only a minimal number of non-specific chromosomal alterations. Our results indicate that HTLV-1 virus is likely not involved in the pathogenesis of classic MF/SS since it drives a very different pathway of lymphomagenesis based on our findings in these cells. This study also provides for the first time a comprehensive characterization of the CTCL cells with respect to gene expression profiling, TP53 mutation status, ability to produce tumors in mice and response to commonly used therapies.",

keywords = "Cutaneous T-cell lymphomas, Gene expression analysis, Human T-cell lymphotropic virus type 1, Spectral karyotyping, Xenograft tumors",

author = "Elena Netchiporouk and Jennifer Gantchev and Matthew Tsang and Philippe Thibault and Watters, {Andrew K.} and Hughes, {John Douglas Matthew} and Ghazawi, {Feras M.} and Anders Woetmann and Niels {\O}dum and Denis Sasseville and Litvinov, {Ivan V.}",

year = "2017",

doi = "10.18632/oncotarget.21619",

language = "English",

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T1 - Analysis of CTCL cell lines reveals important differences between mycosis fungoides/Sézary syndrome vs. HTLV-1+ leukemic cell lines

AU - Netchiporouk, Elena

AU - Gantchev, Jennifer

AU - Tsang, Matthew

AU - Thibault, Philippe

AU - Watters, Andrew K.

AU - Hughes, John Douglas Matthew

AU - Ghazawi, Feras M.

AU - Woetmann, Anders

AU - Ødum, Niels

AU - Sasseville, Denis

AU - Litvinov, Ivan V.

PY - 2017

Y1 - 2017

N2 - HTLV-1 is estimated to affect ~20 million people worldwide and in ~5% of carriers it produces Adult T-Cell Leukemia/Lymphoma (ATLL), which can often masquerade and present with classic erythematous pruritic patches and plaques that are typically seen in Mycosis Fungoides (MF) and Sézary Syndrome (SS), the most recognized variants of Cutaneous T-Cell Lymphomas (CTCL). For many years the role of HTLV- 1 in the pathogenesis of MF/SS has been hotly debated. In this study we analyzed CTCL vs. HTLV-1+ leukemic cells. We performed G-banding/spectral karyotyping, extensive gene expression analysis, TP53 sequencing in the 11 patient-derived HTLV- 1+ (MJ and Hut102) vs. HTLV-1- (Myla, Mac2a, PB2B, HH, H9, Hut78, SZ4, Sez4 and SeAx) CTCL cell lines. We further tested drug sensitivities to commonly used CTCL therapies and studied the ability of these cells to produce subcutaneous xenograft tumors in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice. Our work demonstrates that unlike classic advanced MF/SS cells that acquire many ongoing balanced and unbalanced chromosomal translocations, HTLV-1+ CTCL leukemia cells are diploid and exhibit only a minimal number of non-specific chromosomal alterations. Our results indicate that HTLV-1 virus is likely not involved in the pathogenesis of classic MF/SS since it drives a very different pathway of lymphomagenesis based on our findings in these cells. This study also provides for the first time a comprehensive characterization of the CTCL cells with respect to gene expression profiling, TP53 mutation status, ability to produce tumors in mice and response to commonly used therapies.

AB - HTLV-1 is estimated to affect ~20 million people worldwide and in ~5% of carriers it produces Adult T-Cell Leukemia/Lymphoma (ATLL), which can often masquerade and present with classic erythematous pruritic patches and plaques that are typically seen in Mycosis Fungoides (MF) and Sézary Syndrome (SS), the most recognized variants of Cutaneous T-Cell Lymphomas (CTCL). For many years the role of HTLV- 1 in the pathogenesis of MF/SS has been hotly debated. In this study we analyzed CTCL vs. HTLV-1+ leukemic cells. We performed G-banding/spectral karyotyping, extensive gene expression analysis, TP53 sequencing in the 11 patient-derived HTLV- 1+ (MJ and Hut102) vs. HTLV-1- (Myla, Mac2a, PB2B, HH, H9, Hut78, SZ4, Sez4 and SeAx) CTCL cell lines. We further tested drug sensitivities to commonly used CTCL therapies and studied the ability of these cells to produce subcutaneous xenograft tumors in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice. Our work demonstrates that unlike classic advanced MF/SS cells that acquire many ongoing balanced and unbalanced chromosomal translocations, HTLV-1+ CTCL leukemia cells are diploid and exhibit only a minimal number of non-specific chromosomal alterations. Our results indicate that HTLV-1 virus is likely not involved in the pathogenesis of classic MF/SS since it drives a very different pathway of lymphomagenesis based on our findings in these cells. This study also provides for the first time a comprehensive characterization of the CTCL cells with respect to gene expression profiling, TP53 mutation status, ability to produce tumors in mice and response to commonly used therapies.

KW - Cutaneous T-cell lymphomas

KW - Gene expression analysis

KW - Human T-cell lymphotropic virus type 1

KW - Spectral karyotyping

KW - Xenograft tumors

U2 - 10.18632/oncotarget.21619

DO - 10.18632/oncotarget.21619

M3 - Journal article

C2 - 29221181

AN - SCOPUS:85033393647

SN - 1949-2553

VL - 8

SP - 95981

EP - 95998

JO - OncoTarget

JF - OncoTarget

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